| 1. |
- Berzina, L., et al.
(författare)
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DR3 is associated with type 1 diabetes and blood group ABO incompatibility
- 2002
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Ingår i: Annals of the New York Academy of Sciences. - : Wiley. - 0077-8923 .- 1749-6632. ; 958, s. 345-348
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 diabetes is associated with autoimmunity against pancreatic β cells. ABO incompatibility is associated with ABO immunization during pregnancy. Type 1 diabetes is associated with certain HLA DR and DQ haplotypes. The mechanism by which blood group incompatibility is associated with the risk of type 1 diabetes is not known. We propose that certain HLA alleles contribute to the development of both type 1 diabetes and ABO blood group incompatibility. We studied 57 children with ABO blood group incompatibility, 118 children with type 1 diabetes, and 98 age- and sex-matched unrelated healthy controls from Linköping. Typing of HLA DQA1, DQB1, and DRB1 was done on DNA extracted from peripheral blood, by PCR amplification, manual dot-blotting onto nylon membranes, synthetic sequence-specific oligonucleotide (SSO) probe 3′ end-labeling with 32P-dCTP, and hybridization followed by stringency washes and autoradiography. We observed that DR3 allele was more frequent in patients with ABO incompatibility when compared to healthy controls (OR = 2.7, Pc < 0.05). Patients with type 1 diabetes had significantly higher frequency of DR3, DQ2, DR4, and DQ8 alleles when compared to healthy controls. No significant difference was observed in frequency of DR3 between ABO blood group incompatibility and type 1 diabetes patients. We conclude that DR3 is associated with both the development of type 1 diabetes and ABO incompatibility.
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| 2. |
- Hanås, Ragnar, 1951, et al.
(författare)
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Indwelling catheters used from the onset of diabetes decrease injection pain and pre-injection anxiety
- 2002
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Ingår i: J Pediatr. - : Elsevier BV. - 0022-3476 .- 0022-3476 .- 1097-6833. ; 140:3, s. 315-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the use of indwelling catheters as injection aids at diabetes onset to reduce injection pain and pre-injection anxiety. STUDY DESIGN: Forty-one patients aged 8.1 +/- 3.7 years (range, 1-15) participated in this open, controlled randomized study. A 10-cm VAS with faces was used for scoring. A local anesthetic cream was used before all insertions. The control group used insulin pens with standard needles. After one week, the indwelling catheter group could choose regular injections but were included in the "intention to treat" analysis. RESULTS: Injection pain and anxiety decreased from day 1 to 15 in both groups (average, 4.1 injections/day). Pain was significantly lower for indwelling catheter injections when scored by parents (median, 1.2 cm vs 2.7 cm; P =.002), children/teenagers (0.8 cm vs 1.5 cm; P =.006), and nurses (1.4 cm vs 3.0 cm; P =.002). Parental pre-injection anxiety was also lower (1.2 cm vs 2.9 cm; P =.016). Taking injections, including inserting catheters, was found to be less problematic with an indwelling catheter (1.6 cm vs 3.3 cm;P =.009). During the 6-month follow-up, injection pain and injection problems were significantly lower in the catheter group. Mean catheter indwelling time was 3.7 days. Median pain for catheter insertion was 2.1 cm and for glucose testing was 0.9 cm. Sixteen of 20 patients continued to use indwelling catheters after 2 weeks, and 9 of 20 after 6 months. CONCLUSIONS: We found an evident relief of pre-injection anxiety and injection pain when using indwelling catheters for introducing insulin injections at the onset of diabetes.
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| 3. |
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| 4. |
- Holmdahl, Rikard, et al.
(författare)
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Arthritis induced in rats with non-immunogenic adjuvants as models for rheumatoid arthritis
- 2001
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Ingår i: Immunological Reviews. - : Wiley. - 1600-065X .- 0105-2896. ; 184
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Forskningsöversikt (refereegranskat)abstract
- Rat models are useful for studies of the pathogenesis of rheumatoid arthritis (RA) since rats are extraordinarily sensitive to induction of arthritis with adjuvants. Injection of not only the classical complete Freund's adjuvant but also mineral oil without mycobacteria and pure adjuvants such as pristane and squalene, induce severe arthritis in many rat strains. Models like pristane-induced arthritis in rats are optimal models for RA since they fulfill the RA criteria including a chronic relapsing disease course. Arthritogenic adjuvants like pristane, avridine, squalene and mineral oil are not immunogenic since they do not contain major histocompatibility complex (MHC) binding peptides. Nevertheless, the diseases are MHC-associated and dependent on the activation of alphabetaTCR (T-cell receptor)-expressing T cells. However, it has not been possible to link the immune response to joint antigens or other endogenous components although immunization with various cartilage proteins induce arthritis but with different pathogeneses. To unravel the mechanisms behind adjuvant-induced arthritis, a disease-oriented genetic approach is optimal. Several loci that control onset of arthritis, severity and chronicity of the disease have been identified in genetic crosses and most of these have been confirmed in congenic strains. In addition, many of these loci are found in other autoimmune models in the rat as well as associated with arthritis in mice and humans.
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| 5. |
- Kullberg, C, et al.
(författare)
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Prevalence of retinopathy differs with age at onset of diabetes in a population of patients with Type 1 diabetes
- 2002
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 19:11, s. 924-931
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Tidskriftsartikel (refereegranskat)abstract
- Aim. The VISS study (Vascular complications in South-east Sweden) investigates prevalence and incidence of vascular complications in a population with Type 1 diabetes, from a well-defined geographical area and followed from diag-nosis with HbA1c measurement. Method. The study population comprised all 440 patients with Type 1 diabetes onset before the age of 36 years, onset during 1983-1987, and at the time of onset living within the counties of J÷nk÷ping, Kalmar or ╓sterg÷tland. Retinopathy was examined with fundus photography 1994-1995, and classified according to a modified Airlie House protocol. Results. Fundus photographs from 390 patients were evaluated. In 277 (71%) patients no retinopathy was seen. The prevalence of retinopathy increased from 11% among patients < 5 years old at diabetes onset, to 48% among those 15-19 years old at diabetes onset, and then decreased to 30% for patients 30-35 years old at diabetes onset (P for ?2 for linear trend for all ages 0.017, for age at onset 0-19 yearsP = 0.0003), without corresponding differences in duration or HbA1c between patients with different onset age. Patients with HbA1c in the highest quartile (> 8.3% HbA1c) had a relative risk of 2.4 (95% confidence) interval (CI) 1.7-3.2) of having any retinopathy compared with patients with lower HbA1c, and a relative risk of 7.1 (95% CI 3.0-16.7) of having other forms of retinopathy than microaneurysms. Conclusion. In patients with diabetes duration of 6-13 years, the prevalence of retinopathy is clearly related to glycaemic control. Furthermore, the risk of retinopathy varies with different age at onset, independently of differences in duration or glycaemic control.
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| 6. |
- Ludvigsson, Johnny, 1943-, et al.
(författare)
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Photopheresis at onset of type 1 diabetes : A randomised, double blind, placebo controlled trial
- 2001
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Ingår i: Archives of Disease in Childhood. - : BMJ. - 0003-9888 .- 1468-2044. ; 85:2, s. 149-154
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Tidskriftsartikel (refereegranskat)abstract
- Background - In recent years photopheresis, an extracorporeal form of photochemotherapy using psoralen and ultraviolet A irradiation of leucocytes, has been claimed to be an effective form of immunomodulation. Aim - To evaluate its effect in type 1 diabetes we performed a double blind, controlled study using placebo tablets and sham pheresis in the control group. Methods - A total of 49 children, aged 10-18 years of age at diagnosis of type 1 diabetes were included, 40 fulfilled the study and were followed for three years (19 received active treatment with photopheresis and 21 placebo treatment). Results - The actively treated children secreted significantly more C peptide in urine during follow up than control children. C peptide values in serum showed corresponding differences between the two groups. The insulin dose/kg body weight needed to achieve satisfactory HbA1c values was always lower in the photopheresis group, there was no difference between the groups regarding HbAlc values during follow up. The treatment was well accepted except for nausea (n = 3) and urticaria (n = 1) in the actively treated group. There were no differences regarding weight or height, or episodes of infection between the two groups during follow up. Conclusion - Photopheresis does have an effect in addition to its possible placebo effect, shown as a weak but significant effect on the disease process at the onset of type 1 diabetes, an effect still noted after three years of follow up.
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| 8. |
- Ortqvist, E., et al.
(författare)
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Temporary preservation of beta-cell function by diazoxide treatment in childhood type 1 diabetes
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 27:9, s. 2191-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We examined the effect of diazoxide, an ATP-sensitive K(+) channel opener and inhibitor of insulin secretion, on beta-cell function and remission in children at clinical onset of type 1 diabetes. RESEARCH DESIGN AND METHODS: A total of 56 subjects (21 girls and 35 boys, age 7-17 years) were randomized to 3 months of active treatment (diazoxide 5-7.5 mg/kg in divided doses) or placebo in addition to multiple daily insulin injections and were followed for 2 years. RESULTS: Diazoxide decreased circulating C-peptide concentrations by approximately 50%. After cessation of the treatment, basal and meal-stimulated C-peptide concentrations increased to a maximum at 6 months, followed by a decline. Meal-stimulated C-peptide concentration was significantly higher at 12 months (0.43 +/- 0.22 vs. 0.31 +/- 0.26 nmol/l, P = 0.018) and tended to fall less from clinical onset to 24 months in the diazoxide- vs. placebo-treated patients (-0.05 +/- 0.24 vs. -0.18 +/- 0.26 nmol/l, P = 0.064). At 24 months, the meal-stimulated C-peptide concentrations were 0.24 +/- 0.20 and 0.20 +/- 0.17 nmol/l, respectively. Side effects of diazoxide were prevalent. CONCLUSIONS: This study demonstrates that partial inhibition of insulin secretion for 3 months at onset of childhood type 1 diabetes suspends the period of remission and temporarily preserves residual insulin production. Further evaluation of the full potential of beta-cell rest will require compounds with less side effects as well as protocols optimized for sustained secretory arrest.
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